CN101827841B - (r)-4-(杂芳基)苯乙基衍生物及其药物组合物 - Google Patents
(r)-4-(杂芳基)苯乙基衍生物及其药物组合物 Download PDFInfo
- Publication number
- CN101827841B CN101827841B CN200880112174XA CN200880112174A CN101827841B CN 101827841 B CN101827841 B CN 101827841B CN 200880112174X A CN200880112174X A CN 200880112174XA CN 200880112174 A CN200880112174 A CN 200880112174A CN 101827841 B CN101827841 B CN 101827841B
- Authority
- CN
- China
- Prior art keywords
- phenyl
- thiazol
- trifluoromethyl
- ethyl
- amino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 49
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims abstract description 17
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims abstract description 17
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 9
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims abstract description 7
- 206010016654 Fibrosis Diseases 0.000 claims abstract description 7
- 206010018364 Glomerulonephritis Diseases 0.000 claims abstract description 7
- 208000027418 Wounds and injury Diseases 0.000 claims abstract description 7
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims abstract description 7
- 230000006378 damage Effects 0.000 claims abstract description 7
- 230000004761 fibrosis Effects 0.000 claims abstract description 7
- 208000014674 injury Diseases 0.000 claims abstract description 7
- 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 6
- 206010034277 Pemphigoid Diseases 0.000 claims abstract description 6
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 6
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims abstract description 6
- 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 6
- 208000000594 bullous pemphigoid Diseases 0.000 claims abstract description 6
- 208000028867 ischemia Diseases 0.000 claims abstract description 6
- 230000002265 prevention Effects 0.000 claims abstract description 6
- 230000010410 reperfusion Effects 0.000 claims abstract description 6
- -1 tetrazole compound Chemical class 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 230000035605 chemotaxis Effects 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 150000003536 tetrazoles Chemical class 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 6
- 150000003852 triazoles Chemical class 0.000 claims description 6
- PXZXTAVGDFWJEH-SECBINFHSA-N 4-methyl-n-[4-[(1r)-1-(2h-tetrazol-5-yl)ethyl]phenyl]-1,3-thiazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(C)N=3)=CC=2)=NN=NN1 PXZXTAVGDFWJEH-SECBINFHSA-N 0.000 claims description 5
- KEBGAGJQQZSMHV-SNVBAGLBSA-N 4-tert-butyl-n-[4-[(1r)-1-(2h-tetrazol-5-yl)ethyl]phenyl]-1,3-thiazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(C)(C)C)=CC=2)=NN=NN1 KEBGAGJQQZSMHV-SNVBAGLBSA-N 0.000 claims description 5
- JZCYGJPMWDIUIJ-MRVPVSSYSA-N 5-[(1r)-1-[4-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]-1,2-oxazol-3-one Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)=CC(O)=NO1 JZCYGJPMWDIUIJ-MRVPVSSYSA-N 0.000 claims description 5
- XLIYNKPPYHDVHC-MRVPVSSYSA-N 5-[(1r)-1-[4-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]-1,2-thiazol-3-one Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)=CC(O)=NS1 XLIYNKPPYHDVHC-MRVPVSSYSA-N 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- NSRDFEDODHRJJA-SSDOTTSWSA-N 4-[(1r)-1-[4-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]-1,2,5-oxadiazol-3-one Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)=NON=C1O NSRDFEDODHRJJA-SSDOTTSWSA-N 0.000 claims description 4
- PWNMDNDIVOXBSU-SSDOTTSWSA-N 4-[(1r)-1-[4-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]-1,2,5-thiadiazol-3-one Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)=NSN=C1O PWNMDNDIVOXBSU-SSDOTTSWSA-N 0.000 claims description 4
- PBGXUWBEWSDLKD-SECBINFHSA-N 4-methyl-n-[4-[(1r)-1-(2h-tetrazol-5-yl)ethyl]phenyl]-1,3-oxazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3OC=C(C)N=3)=CC=2)=NN=NN1 PBGXUWBEWSDLKD-SECBINFHSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- HJCSELXWCNTCBX-SNVBAGLBSA-N n-[4-[(1r)-1-(2-hydroxy-4-methylpyrazol-3-yl)ethyl]phenyl]-4-(trifluoromethyl)-1,3-thiazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)=C(C)C=NN1O HJCSELXWCNTCBX-SNVBAGLBSA-N 0.000 claims description 4
- ANJBIEBLHPUZNB-SECBINFHSA-N n-[4-[(1r)-1-(2-hydroxypyrazol-3-yl)ethyl]phenyl]-4-(trifluoromethyl)-1,3-thiazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)=CC=NN1O ANJBIEBLHPUZNB-SECBINFHSA-N 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical group C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 3
- 150000003217 pyrazoles Chemical class 0.000 claims description 3
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical group C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 3
- 150000004867 thiadiazoles Chemical class 0.000 claims description 3
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 claims description 3
- RCKAGEAESHXMIH-MRVPVSSYSA-N 4-methyl-5-[(1r)-1-[4-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]-1,2-oxazol-3-one Chemical compound C=1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)ON=C(O)C=1C RCKAGEAESHXMIH-MRVPVSSYSA-N 0.000 claims description 2
- 150000003854 isothiazoles Chemical class 0.000 claims description 2
- 150000002545 isoxazoles Chemical class 0.000 claims description 2
- NZXOOPPMMVMGAQ-MRVPVSSYSA-N n-[4-[(1r)-1-(2-hydroxy-1,2,4-triazol-3-yl)ethyl]phenyl]-4-(trifluoromethyl)-1,3-thiazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)=NC=NN1O NZXOOPPMMVMGAQ-MRVPVSSYSA-N 0.000 claims description 2
- OXJPICCVZKNYLU-MRVPVSSYSA-N n-[4-[(1r)-1-(3-hydroxytriazol-4-yl)ethyl]phenyl]-4-(trifluoromethyl)-1,3-thiazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)=CN=NN1O OXJPICCVZKNYLU-MRVPVSSYSA-N 0.000 claims description 2
- 150000004866 oxadiazoles Chemical class 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 210000003622 mature neutrocyte Anatomy 0.000 claims 1
- 230000003399 chemotactic effect Effects 0.000 abstract description 14
- 230000000295 complement effect Effects 0.000 abstract description 10
- 230000004913 activation Effects 0.000 abstract description 9
- 210000000440 neutrophil Anatomy 0.000 abstract description 7
- 230000005764 inhibitory process Effects 0.000 abstract description 6
- 210000001616 monocyte Anatomy 0.000 abstract description 6
- 230000007170 pathology Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 51
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 37
- 238000005160 1H NMR spectroscopy Methods 0.000 description 36
- 239000000203 mixture Substances 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 29
- 239000007832 Na2SO4 Substances 0.000 description 28
- 229910052938 sodium sulfate Inorganic materials 0.000 description 28
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 25
- 239000007787 solid Substances 0.000 description 25
- 239000000543 intermediate Substances 0.000 description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 24
- 239000012043 crude product Substances 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
- 238000001704 evaporation Methods 0.000 description 21
- 230000008020 evaporation Effects 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 239000003921 oil Substances 0.000 description 19
- 235000019198 oils Nutrition 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
- 238000001816 cooling Methods 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
- 239000000460 chlorine Chemical group 0.000 description 14
- 238000001035 drying Methods 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 8
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 238000002955 isolation Methods 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 102100032957 C5a anaphylatoxin chemotactic receptor 1 Human genes 0.000 description 7
- 101710098483 C5a anaphylatoxin chemotactic receptor 1 Proteins 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- OUGCUPYREMACGK-SSDOTTSWSA-N (2r)-2-[4-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino]phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1NC1=NC(C(F)(F)F)=CS1 OUGCUPYREMACGK-SSDOTTSWSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 235000019260 propionic acid Nutrition 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
- JGVJWGNYTIXBSA-UHFFFAOYSA-N OC1=CC=NS1 Chemical compound OC1=CC=NS1 JGVJWGNYTIXBSA-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical group 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 150000004702 methyl esters Chemical class 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
- 238000005903 acid hydrolysis reaction Methods 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000002158 endotoxin Substances 0.000 description 4
- 229920006008 lipopolysaccharide Polymers 0.000 description 4
- ANDGBIBENVSINF-SSDOTTSWSA-N n-[4-[(1r)-1-(2h-tetrazol-5-yl)ethyl]phenyl]-4-(trifluoromethyl)-1,3-thiazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)=NN=NN1 ANDGBIBENVSINF-SSDOTTSWSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 3
- MLPAIIATLGUTEE-UHFFFAOYSA-N 1,3-thiazol-5-ol Chemical compound OC1=CN=CS1 MLPAIIATLGUTEE-UHFFFAOYSA-N 0.000 description 3
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 3
- WDVKRSISZOEOCI-UCWRFOARSA-N 4-methyl-5-[(1r)-1-[4-[[5-(trifluoromethyl)-2h-pyrrol-2-yl]amino]phenyl]ethyl]-1,2-oxazol-3-one Chemical compound C=1([C@H](C)C=2C=CC(NC3N=C(C=C3)C(F)(F)F)=CC=2)ON=C(O)C=1C WDVKRSISZOEOCI-UCWRFOARSA-N 0.000 description 3
- 108010089414 Anaphylatoxins Proteins 0.000 description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 150000003871 sulfonates Chemical class 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 3
- FDCNKYFUHVZCSP-SECBINFHSA-N (2r)-2-[4-[(4-methyl-1,3-thiazol-2-yl)amino]phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1NC1=NC(C)=CS1 FDCNKYFUHVZCSP-SECBINFHSA-N 0.000 description 2
- LPPNMWHZIUTUIZ-SSDOTTSWSA-N (2r)-2-[4-[[4-(trifluoromethyl)-1,3-oxazol-2-yl]amino]phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1NC1=NC(C(F)(F)F)=CO1 LPPNMWHZIUTUIZ-SSDOTTSWSA-N 0.000 description 2
- RHBNSXIKWAVKHF-MRVPVSSYSA-N (4r)-3-oxo-4-[4-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino]phenyl]pentanoic acid Chemical compound C1=CC([C@H](C(=O)CC(O)=O)C)=CC=C1NC1=NC(C(F)(F)F)=CS1 RHBNSXIKWAVKHF-MRVPVSSYSA-N 0.000 description 2
- FUOSTELFLYZQCW-UHFFFAOYSA-N 1,2-oxazol-3-one Chemical compound OC=1C=CON=1 FUOSTELFLYZQCW-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- ONZQYZKCUHFORE-UHFFFAOYSA-N 3-bromo-1,1,1-trifluoropropan-2-one Chemical compound FC(F)(F)C(=O)CBr ONZQYZKCUHFORE-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 108010028773 Complement C5 Proteins 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 230000004154 complement system Effects 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical class OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 2
- SKCXULLGLCQCGY-MRVPVSSYSA-N n-[4-[(1r)-1-(2h-tetrazol-5-yl)ethyl]phenyl]-1,3-thiazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=CN=3)=CC=2)=NN=NN1 SKCXULLGLCQCGY-MRVPVSSYSA-N 0.000 description 2
- PVHCLSVFJAHYFY-SSDOTTSWSA-N n-[4-[(1r)-1-(2h-tetrazol-5-yl)ethyl]phenyl]-4-(trifluoromethyl)-1,3-oxazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3OC=C(N=3)C(F)(F)F)=CC=2)=NN=NN1 PVHCLSVFJAHYFY-SSDOTTSWSA-N 0.000 description 2
- 230000011242 neutrophil chemotaxis Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- NDLIRBZKZSDGSO-UHFFFAOYSA-N tosyl azide Chemical compound CC1=CC=C(S(=O)(=O)[N-][N+]#N)C=C1 NDLIRBZKZSDGSO-UHFFFAOYSA-N 0.000 description 2
- YGXRRPHYTREVQT-MRVPVSSYSA-N (2r)-2-[4-(1,3-thiazol-2-ylamino)phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1NC1=NC=CS1 YGXRRPHYTREVQT-MRVPVSSYSA-N 0.000 description 1
- PEWMCDTVGCALBX-SNVBAGLBSA-N (2r)-2-[4-[(4-tert-butyl-1,3-thiazol-2-yl)amino]phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1NC1=NC(C(C)(C)C)=CS1 PEWMCDTVGCALBX-SNVBAGLBSA-N 0.000 description 1
- RYWJTDRIOBOVTB-QMMMGPOBSA-N (2r)-2-[4-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino]phenyl]propanenitrile Chemical compound C1=CC([C@H](C#N)C)=CC=C1NC1=NC(C(F)(F)F)=CS1 RYWJTDRIOBOVTB-QMMMGPOBSA-N 0.000 description 1
- AKGDDBYQRAYOME-SSDOTTSWSA-N (2r)-2-[4-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino]phenyl]propanimidamide Chemical compound C1=CC([C@H](C(N)=N)C)=CC=C1NC1=NC(C(F)(F)F)=CS1 AKGDDBYQRAYOME-SSDOTTSWSA-N 0.000 description 1
- OXOVIDVRVOXOLB-RZZZFEHKSA-N (3r)-2-(hydroxyamino)-3-[4-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino]phenyl]butanenitrile Chemical compound C1=CC([C@H](C(NO)C#N)C)=CC=C1NC1=NC(C(F)(F)F)=CS1 OXOVIDVRVOXOLB-RZZZFEHKSA-N 0.000 description 1
- AKWPIEROWUWWKT-RZZZFEHKSA-N (3r)-2-amino-3-[4-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino]phenyl]butanenitrile Chemical compound C1=CC([C@H](C(N)C#N)C)=CC=C1NC1=NC(C(F)(F)F)=CS1 AKWPIEROWUWWKT-RZZZFEHKSA-N 0.000 description 1
- JSNGJBRSCDNQTL-QVDQXJPCSA-N (4r)-2-methyl-3-oxo-4-[4-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino]phenyl]pentanal Chemical compound C1=CC([C@@H](C)C(=O)C(C=O)C)=CC=C1NC1=NC(C(F)(F)F)=CS1 JSNGJBRSCDNQTL-QVDQXJPCSA-N 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical group NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- KJMCAXYHYPDRAV-UHFFFAOYSA-N 2,2,5-trimethyl-1,3-dioxane-4,6-dione Chemical compound CC1C(=O)OC(C)(C)OC1=O KJMCAXYHYPDRAV-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- XYVMOLOUBJBNBF-UHFFFAOYSA-N 3h-1,3-oxazol-2-one Chemical class OC1=NC=CO1 XYVMOLOUBJBNBF-UHFFFAOYSA-N 0.000 description 1
- 125000006418 4-methylphenylsulfonyl group Chemical group 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 101001027327 Bos taurus Growth-regulated protein homolog alpha Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 102000001327 Chemokine CCL5 Human genes 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- 102000016950 Chemokine CXCL1 Human genes 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108010028780 Complement C3 Proteins 0.000 description 1
- 102000016574 Complement C3-C5 Convertases Human genes 0.000 description 1
- 108010067641 Complement C3-C5 Convertases Proteins 0.000 description 1
- 108010028778 Complement C4 Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 101001039702 Escherichia coli (strain K12) Methyl-accepting chemotaxis protein I Proteins 0.000 description 1
- 208000021203 Glomerular vascular disease Diseases 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 101001055222 Homo sapiens Interleukin-8 Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 102000009490 IgG Receptors Human genes 0.000 description 1
- 108010073807 IgG Receptors Proteins 0.000 description 1
- 102100026236 Interleukin-8 Human genes 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 102000004890 Interleukin-8 Human genes 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 208000003456 Juvenile Arthritis Diseases 0.000 description 1
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 208000035977 Rare disease Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003367 anti-collagen effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000006041 cell recruitment Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Chemical group 0.000 description 1
- 208000019069 chronic childhood arthritis Diseases 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- LGHBWYKFMKMPMU-UHFFFAOYSA-N dimethyl propan-2-yl phosphate Chemical compound COP(=O)(OC)OC(C)C LGHBWYKFMKMPMU-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000000224 granular leucocyte Anatomy 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 239000000815 hypotonic solution Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- MGIYRDNGCNKGJU-UHFFFAOYSA-N isothiazolinone Chemical compound O=C1C=CSN1 MGIYRDNGCNKGJU-UHFFFAOYSA-N 0.000 description 1
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000001865 kupffer cell Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- HXAMUXFIQLEMOM-SSDOTTSWSA-N methyl (2r)-2-[4-(carbamoylamino)phenyl]propanoate Chemical compound COC(=O)[C@H](C)C1=CC=C(NC(N)=O)C=C1 HXAMUXFIQLEMOM-SSDOTTSWSA-N 0.000 description 1
- 230000028550 monocyte chemotaxis Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- RISBRASDXYBPAW-MRVPVSSYSA-N n-[4-[(1r)-1-(1h-1,2,4-triazol-5-yl)ethyl]phenyl]-4-(trifluoromethyl)-1,3-thiazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)=NC=NN1 RISBRASDXYBPAW-MRVPVSSYSA-N 0.000 description 1
- YKSSZGJYJQHLKZ-SECBINFHSA-N n-[4-[(1r)-1-(1h-pyrazol-5-yl)ethyl]phenyl]-4-(trifluoromethyl)-1,3-thiazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)=CC=NN1 YKSSZGJYJQHLKZ-SECBINFHSA-N 0.000 description 1
- NYHWRPLPOOLDNP-MRVPVSSYSA-N n-[4-[(1r)-1-(2h-triazol-4-yl)ethyl]phenyl]-4-(trifluoromethyl)-1,3-thiazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)=CN=NN1 NYHWRPLPOOLDNP-MRVPVSSYSA-N 0.000 description 1
- DKLVEGKYLYZJNG-SSDOTTSWSA-N n-[4-[(1r)-1-(4-chloro-1,2,5-thiadiazol-3-yl)ethyl]phenyl]-4-(trifluoromethyl)-1,3-thiazol-2-amine Chemical compound C1([C@H](C)C=2C=CC(NC=3SC=C(N=3)C(F)(F)F)=CC=2)=NSN=C1Cl DKLVEGKYLYZJNG-SSDOTTSWSA-N 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002916 oxazoles Chemical group 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- GNFWGDKKNWGGJY-UHFFFAOYSA-N propanimidamide Chemical compound CCC(N)=N GNFWGDKKNWGGJY-UHFFFAOYSA-N 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- OKAFFHNXRJQQET-UHFFFAOYSA-N tert-butylazanium;fluoride;trihydrate Chemical compound O.O.O.[F-].CC(C)(C)[NH3+] OKAFFHNXRJQQET-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003557 thiazoles Chemical group 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07020396 | 2007-10-18 | ||
| EP07020396.3 | 2007-10-18 | ||
| PCT/EP2008/064023 WO2009050258A1 (en) | 2007-10-18 | 2008-10-17 | (r)-4-(heteroaryl) phenylethyl derivatives and pharmaceutical compositions containing them |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101827841A CN101827841A (zh) | 2010-09-08 |
| CN101827841B true CN101827841B (zh) | 2012-11-28 |
Family
ID=40325746
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200880112174XA Active CN101827841B (zh) | 2007-10-18 | 2008-10-17 | (r)-4-(杂芳基)苯乙基衍生物及其药物组合物 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US8133911B2 (pt) |
| EP (1) | EP2201006B1 (pt) |
| JP (1) | JP5374511B2 (pt) |
| CN (1) | CN101827841B (pt) |
| AT (1) | ATE501140T1 (pt) |
| AU (1) | AU2008313669B2 (pt) |
| BR (1) | BRPI0817824B8 (pt) |
| CA (1) | CA2702307C (pt) |
| DE (1) | DE602008005488D1 (pt) |
| DK (1) | DK2201006T3 (pt) |
| ES (1) | ES2361233T3 (pt) |
| HK (1) | HK1146723A1 (pt) |
| HR (1) | HRP20110406T1 (pt) |
| IL (1) | IL205029A (pt) |
| PL (1) | PL2201006T3 (pt) |
| PT (1) | PT2201006E (pt) |
| RU (1) | RU2475486C2 (pt) |
| SI (1) | SI2201006T1 (pt) |
| WO (1) | WO2009050258A1 (pt) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2166006A1 (en) * | 2008-09-18 | 2010-03-24 | Dompe' S.P.A. | 2-aryl-propionic acids and derivatives and pharmaceutical compositions containing them |
| EP3498269A1 (en) * | 2017-12-12 | 2019-06-19 | Dompé farmaceutici S.p.A. | C5ar inhibitors for use in the treatment of chemotherapy-induced iatrogenic pain |
| CN115433143B (zh) * | 2021-06-03 | 2023-10-13 | 中国科学院大连化学物理研究所 | 一种异噻唑啉酮类化合物的合成方法 |
| EP4397306A1 (en) | 2023-01-05 | 2024-07-10 | Dompe' Farmaceutici S.P.A. | C5ar1 inhibitors for use in the treatment of ocular mucous membrane pemphigoid and/or oral mucous membrane pemphigoid |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003029187A1 (en) * | 2001-09-28 | 2003-04-10 | Dompe S.P.A. | Quaternary ammonium salts of omega-aminoalkylamides of r-2-aryl-propionic acids and pharmaceutical compositions containing them |
| WO2007060215A2 (en) * | 2005-11-24 | 2007-05-31 | Dompe' Pha.R.Ma S.P.A. | (r)-arylkylamino derivatives and pharmaceutical compositions containing them |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR9710002A (pt) * | 1996-06-27 | 1999-08-10 | Janssen Pharmaceutica Nv | N-[4-(heteroarilmetil)fenil]-heteroarilaminas |
-
2008
- 2008-10-17 PT PT08840589T patent/PT2201006E/pt unknown
- 2008-10-17 JP JP2010529394A patent/JP5374511B2/ja active Active
- 2008-10-17 WO PCT/EP2008/064023 patent/WO2009050258A1/en active Application Filing
- 2008-10-17 PL PL08840589T patent/PL2201006T3/pl unknown
- 2008-10-17 RU RU2010119705/04A patent/RU2475486C2/ru active
- 2008-10-17 SI SI200830268T patent/SI2201006T1/sl unknown
- 2008-10-17 ES ES08840589T patent/ES2361233T3/es active Active
- 2008-10-17 CA CA2702307A patent/CA2702307C/en active Active
- 2008-10-17 US US12/681,841 patent/US8133911B2/en active Active
- 2008-10-17 AU AU2008313669A patent/AU2008313669B2/en active Active
- 2008-10-17 DK DK08840589.9T patent/DK2201006T3/da active
- 2008-10-17 EP EP08840589A patent/EP2201006B1/en active Active
- 2008-10-17 CN CN200880112174XA patent/CN101827841B/zh active Active
- 2008-10-17 DE DE602008005488T patent/DE602008005488D1/de active Active
- 2008-10-17 BR BRPI0817824A patent/BRPI0817824B8/pt active IP Right Grant
- 2008-10-17 AT AT08840589T patent/ATE501140T1/de not_active IP Right Cessation
-
2010
- 2010-04-12 IL IL205029A patent/IL205029A/en active IP Right Grant
-
2011
- 2011-01-27 HK HK11100835.6A patent/HK1146723A1/xx unknown
- 2011-05-31 HR HR20110406T patent/HRP20110406T1/hr unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003029187A1 (en) * | 2001-09-28 | 2003-04-10 | Dompe S.P.A. | Quaternary ammonium salts of omega-aminoalkylamides of r-2-aryl-propionic acids and pharmaceutical compositions containing them |
| WO2007060215A2 (en) * | 2005-11-24 | 2007-05-31 | Dompe' Pha.R.Ma S.P.A. | (r)-arylkylamino derivatives and pharmaceutical compositions containing them |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009050258A1 (en) | 2009-04-23 |
| DE602008005488D1 (de) | 2011-04-21 |
| JP5374511B2 (ja) | 2013-12-25 |
| BRPI0817824B1 (pt) | 2018-12-26 |
| HK1146723A1 (en) | 2011-07-08 |
| AU2008313669B2 (en) | 2014-01-16 |
| SI2201006T1 (sl) | 2011-07-29 |
| IL205029A0 (en) | 2010-11-30 |
| BRPI0817824B8 (pt) | 2021-05-25 |
| JP2011500643A (ja) | 2011-01-06 |
| BRPI0817824A2 (pt) | 2015-03-31 |
| RU2475486C2 (ru) | 2013-02-20 |
| US20100249198A1 (en) | 2010-09-30 |
| PT2201006E (pt) | 2011-05-05 |
| PL2201006T3 (pl) | 2011-08-31 |
| CN101827841A (zh) | 2010-09-08 |
| ATE501140T1 (de) | 2011-03-15 |
| ES2361233T3 (es) | 2011-06-15 |
| CA2702307A1 (en) | 2009-04-23 |
| IL205029A (en) | 2014-09-30 |
| CA2702307C (en) | 2016-04-05 |
| AU2008313669A1 (en) | 2009-04-23 |
| EP2201006B1 (en) | 2011-03-09 |
| RU2010119705A (ru) | 2011-11-27 |
| DK2201006T3 (da) | 2011-06-27 |
| HRP20110406T1 (hr) | 2011-06-30 |
| US8133911B2 (en) | 2012-03-13 |
| EP2201006A1 (en) | 2010-06-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6602895B2 (en) | Inhibitors of factor Xa with a neutral P1 specificity group | |
| JP5225076B2 (ja) | チアゾール環を含むカルボン酸誘導体の医薬用途 | |
| US8207204B2 (en) | Triazole derivatives as SCD inhibitors | |
| US8507690B2 (en) | Thiazole derivative and use thereof as VAP-1 inhibitor | |
| JP4939226B2 (ja) | チアゾール環を含むカルボン酸誘導体およびその医薬用途 | |
| US7863283B2 (en) | Sulphoximine-substituted quinazoline derivatives as immuno-modulators, their preparation and use as medicaments | |
| JP2000502702A (ja) | 抗ヘルペスウイルス性を有するフェニルチアゾール誘導体 | |
| CN1297441A (zh) | 用作为钙蛋白酶抑制剂的杂环取代酰胺 | |
| CA2290982A1 (en) | Inhibitors of factor xa with a neutral p1 specificity group | |
| NO314503B1 (no) | N-Heteroarylpyridinsulfonamidderivater, anvendelse og fremstilling derav samt farmasöytisk preparat | |
| AU2003250496A1 (en) | Hetero biaryl derivatives as matrix metalloproteinase inhibitors | |
| CN101827841B (zh) | (r)-4-(杂芳基)苯乙基衍生物及其药物组合物 | |
| JP2006528630A (ja) | ジフェニル置換シクロアルカン類、そのような化合物を含む組成物、ならびに使用方法 | |
| US20080114003A1 (en) | Pyrimidinylisoxazole Derivatives | |
| EA007718B1 (ru) | Новые соединения гетероциклического оксима, способ их получения и фармацевтические композиции, содержащие их | |
| JP2003505367A (ja) | マトリックスメタロプロテイナーゼ阻害剤としての３−アリールスルホニル−２−（置換メチル）プロパン酸誘導体 | |
| JP3714633B2 (ja) | ２−アミノアゾール誘導体 | |
| CN107001351B (zh) | 可用于治疗特别是糖尿病的2-(1,2,4-三唑-3-基硫烷基)-n-1,3,4-噻二唑-2-基乙酰胺的衍生物 | |
| NZ522968A (en) | 2-aminothiazoline derivatives and their use as NO-synthase inhibitors | |
| CA3162388A1 (en) | 4-phenyl-n-(phenyl)thiazol-2-amine derivatives and related compounds as aryl hydrocarbon receptor (ahr) agonists for the treatment of e.g. angiogenesis implicated or inflammatory disorder | |
| JPH07242646A (ja) | ２−［４−（置換アミジノ）ベンゾイルイミノ］チアゾリン誘導体 | |
| JP2002541256A (ja) | 新規エンドセリン転換酵素阻害剤、その製造および使用 | |
| WO2001047895A1 (fr) | Nouveaux composes comprenant des cycles heteroaromatiques a cinq chainons | |
| JPH0912554A (ja) | フェノキシ酢酸誘導体及びこれを含有する医薬製剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1146723 Country of ref document: HK |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1146723 Country of ref document: HK |
|
| ASS | Succession or assignment of patent right |
Owner name: DOMP PHARMACEUTICAL COMPANY Free format text: FORMER OWNER: DOMPE SPA Effective date: 20150909 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20150909 Address after: Milan Italy Patentee after: DOMPE SPA Address before: Italy City Patentee before: Dompe SPA |